AGTR2 gene polymorphism is associated with muscle fibre composition, athletic status and aerobic performance

New Findings What is the central question of this study? Variations in genes are considered to be molecular determinants maintaining the expression of the slow or fast myosin heavy chains of adult skeletal muscle. The role of polymorphisms of candidate genes involved in skeletal muscle development, energy homeostasis and thyroid and calcium metabolism in the determination of muscle fibre type has not previously been reported. What is the main finding and its importance? We show that the AGTR2 rs11091046 Callele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance. Such findings have important implications for our understanding of muscle function in both health and disease. Muscle fibre type is a heritable trait and can partly predict athletic success. It has been proposed that polymorphisms of genes involved in the regulation of muscle fibre characteristics may predispose the muscle precursor cells of a given individual to be predominantly fast or slow. In the present study, we examined the association between 15 candidate gene polymorphisms and muscle fibre type composition of the vastus lateralis muscle in 55 physically active, healthy men. We found that rs11091046 Callele carriers of the angiotensinII type2 receptor gene (AGTR2; involved in skeletal muscle development, metabolism and circulatory homeostasis) had a significantly higher percentage of slow-twitch fibres than Aallele carriers [54.2(11.1) versus 45.2(10.2)%; P=0.003]. These data indicate that 15.2% of the variation in muscle fibre composition of the vastus lateralis muscle can be explained by the AGTR2 genotype. Next, we investigated the frequencies of the AGTR2 alleles in 2178 Caucasian athletes and 1220 control subjects. The frequency of the AGTR2 Callele was significantly higher in male and female endurance athletes compared with power athletes (males, 62.7 versus 51.7%, P=0.0038; females, 56.6 versus 48.1%, P=0.0169) and control subjects (males, 62.7 versus 51.0%, P=0.0006; elite female athletes, 65.1 versus 55.2%, P=0.0488). Furthermore, the frequency of the AGTR2 Aallele was significantly over-represented in female power athletes (51.9%) in comparison to control subjects (44.8%, P=0.0069). We also found that relative maximal oxygen consumption was significantly greater in male endurance athletes with the AGTR2 Callele compared with AGTR2 Aallele carriers [n=28; 62.3(4.4) versus 57.4(6.0)mlmin(-1)kg(-1); P=0.0197]. Taken together, these results demonstrate that the AGTR2 gene Callele is associated with an increased proportion of slow-twitch muscle fibres, endurance athlete status and aerobic performance, while the Aallele is associated with a higher percentage of fast-twitch fibres and power-oriented disciplines.